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Association of Residual Urine Output with Mortality, Quality of Life, and Inflammation in Incident Hemodialysis The Choices for Healthy Outcomes in caring for End-Stage Renal Disease (CHOICE) Study Peter Schrier, MD Journal Club Hofstra North Shore LIJ School of Medicine 2011
Outline Residual Renal Function What it is Why it matters Peritoneal Dialysis Data Hemodialysis Data CHOICE Study
Residual Renal Function Small Solute Clearance (measured GFR) Volume Clearance (Urine output/volume) Endocrine Kidney (ESA usage, hemoglobin)
Residual Renal Function AY-M Wang & K-N Lai, Kidney International (2006) 69, 1726–1732
Residual Renal Function Mortality All-cause mortality Cardiovascular Quality of Life Overall QoL Fewer diet restrictions Less volume restriction Others (sleep, pain, perceived disease burden, etc.)
RKF and Morality in PD ,[object Object]
965 person, multicenter, prospective, randomized controlled trial
Follow-up at least 2 years
RCT was to measure mortality with standard PD dose vs. more intense PD dose with greater pCrCl (peritoneal creatinine clearance)
Looked at other factors that correlated with mortality, including  rCrCl (renal creatinine clearance),[object Object]
RKF and Morality in PD ,[object Object]
413 person, multicenter, prospective, observational, cohort study of incident PD patients
Mortality with increased rGFR (renal GFR = RKF) vs. increased pCrCl (peritoneal creatinine clearance)NECOSAD-2- Am J Kidney Dis. 2003;41(6):1293- 1302.
RKF and Mortality in PD NECOSAD-2- Am J Kidney Dis. 2003;41(6):1293- 1302.
RKF and Morality in PD ,[object Object]
680 person, multicenter, prospective cohort study
2-year follow-up
Reanalysis of data
Mortality with increased rGFR (renal GFR = RKF) vs. increased pCrCl (peritoneal creatinine clearance) vs. urine outputCANUSA- J Am Soc Nephrol 12: 2158–2162, 2001
RKF and Morality in PD CANUSA- J Am Soc Nephrol 12: 2158–2162, 2001
RKF and Morality in PD CANUSA- J Am Soc Nephrol 12: 2158–2162, 2001
RKF and Mortality in HD ,[object Object]
114 person, single center, prospective cohort study
2-year follow-up
Mortality in patients with vs without RKF
Residual renal function defined as producing       > 100cc urine / 24 hour urine collection
Patients included all current patients at the single hemodialysis center who agreed to participate and RFK was assessed at study initiation onlyShemin-  Am J Kidney Dis. 2001;38(1):85-90.
RKF and Mortality in HD Shemin-  Am J Kidney Dis. 2001;38(1):85-90.
RKF and Mortality in HD Shemin-  Am J Kidney Dis. 2001;38(1):85-90.
RKF and Mortality in HD ,[object Object]
740-person, prospective, observational multicenter cohort study
Incident ESRD patients
Median follow-up 1.7 yearsJ Am Soc Nephrol 15: 1061–1070, 2004
RKF and Mortality in HD Figure 1. The effect of single-pool Kt/Vurea (sp-dKt/Vurea) on mortality by presence of residual renal function (rKt/Vurea = 0 [“anurics’” versus rKt/Vurea >0). The rKt/Vurea and sp-dKt/Vurea were included as time-dependent variables. The relative risks are adjusted for age, Davies’ comorbidity score, primary kidney disease, subjective global assessment, and body mass index. J Am Soc Nephrol 15: 1061–1070, 2004
RKF and Mortality in HD J Am Soc Nephrol 15: 1061–1070, 2004

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Journal Club: Residual renal function

  • 1. Association of Residual Urine Output with Mortality, Quality of Life, and Inflammation in Incident Hemodialysis The Choices for Healthy Outcomes in caring for End-Stage Renal Disease (CHOICE) Study Peter Schrier, MD Journal Club Hofstra North Shore LIJ School of Medicine 2011
  • 2. Outline Residual Renal Function What it is Why it matters Peritoneal Dialysis Data Hemodialysis Data CHOICE Study
  • 3. Residual Renal Function Small Solute Clearance (measured GFR) Volume Clearance (Urine output/volume) Endocrine Kidney (ESA usage, hemoglobin)
  • 4. Residual Renal Function AY-M Wang & K-N Lai, Kidney International (2006) 69, 1726–1732
  • 5. Residual Renal Function Mortality All-cause mortality Cardiovascular Quality of Life Overall QoL Fewer diet restrictions Less volume restriction Others (sleep, pain, perceived disease burden, etc.)
  • 6.
  • 7. 965 person, multicenter, prospective, randomized controlled trial
  • 9. RCT was to measure mortality with standard PD dose vs. more intense PD dose with greater pCrCl (peritoneal creatinine clearance)
  • 10.
  • 11.
  • 12. 413 person, multicenter, prospective, observational, cohort study of incident PD patients
  • 13. Mortality with increased rGFR (renal GFR = RKF) vs. increased pCrCl (peritoneal creatinine clearance)NECOSAD-2- Am J Kidney Dis. 2003;41(6):1293- 1302.
  • 14. RKF and Mortality in PD NECOSAD-2- Am J Kidney Dis. 2003;41(6):1293- 1302.
  • 15.
  • 16. 680 person, multicenter, prospective cohort study
  • 19. Mortality with increased rGFR (renal GFR = RKF) vs. increased pCrCl (peritoneal creatinine clearance) vs. urine outputCANUSA- J Am Soc Nephrol 12: 2158–2162, 2001
  • 20. RKF and Morality in PD CANUSA- J Am Soc Nephrol 12: 2158–2162, 2001
  • 21. RKF and Morality in PD CANUSA- J Am Soc Nephrol 12: 2158–2162, 2001
  • 22.
  • 23. 114 person, single center, prospective cohort study
  • 25. Mortality in patients with vs without RKF
  • 26. Residual renal function defined as producing > 100cc urine / 24 hour urine collection
  • 27. Patients included all current patients at the single hemodialysis center who agreed to participate and RFK was assessed at study initiation onlyShemin- Am J Kidney Dis. 2001;38(1):85-90.
  • 28. RKF and Mortality in HD Shemin- Am J Kidney Dis. 2001;38(1):85-90.
  • 29. RKF and Mortality in HD Shemin- Am J Kidney Dis. 2001;38(1):85-90.
  • 30.
  • 31. 740-person, prospective, observational multicenter cohort study
  • 33. Median follow-up 1.7 yearsJ Am Soc Nephrol 15: 1061–1070, 2004
  • 34. RKF and Mortality in HD Figure 1. The effect of single-pool Kt/Vurea (sp-dKt/Vurea) on mortality by presence of residual renal function (rKt/Vurea = 0 [“anurics’” versus rKt/Vurea >0). The rKt/Vurea and sp-dKt/Vurea were included as time-dependent variables. The relative risks are adjusted for age, Davies’ comorbidity score, primary kidney disease, subjective global assessment, and body mass index. J Am Soc Nephrol 15: 1061–1070, 2004
  • 35. RKF and Mortality in HD J Am Soc Nephrol 15: 1061–1070, 2004
  • 36. RKD and Mortality in Dialysis Pearl and Bargman, Am J Kidney Dis 53:1068-1081
  • 37. Quality of Life (QoL) in PD NECOSAD-2- Am J Kidney Dis. 2003;41(6):1293- 1302.
  • 38. CHOICE STUDY 734 patients from 81 clinics nationally Prospective, observational cohort study Incident dialysis patients New onset of long-term dialysis Baseline at within after initiation of therapy Goal: Determine association of urine output with mortality, quality of life, and inflammation in incident HD patients
  • 39. Assessment of RKF Urine output used as a surrogate for RKF Questionnaire at baseline and one year “Do you produce at least one full cup (250cc) of urine daily?” Urine output was measured in 42% of patients and was found to correlate well with reported production of 250cc/day
  • 43. All-Cause Mortality e Clinical and treatment factors in addition to demographic characteristics: smoking history (ever smoked), pulse pressure, body mass index, primary cause of kidney failure (diabetes, hypertension, glomerulonephritis, or other), Index of Coexistent Disease score (0-3), cardiovascular disease, congestive heart failure, left ventricular hypertrophy, diabetes, and serum albumin level (at baseline or year 1).
  • 44. All-Cause Mortality All-cause Mortality by baseline urine output All-cause Mortality by one-year urine output
  • 45. Cardiovascular Mortality e Clinical and treatment factors in addition to demographic characteristics: smoking history (ever smoked), pulse pressure, body mass index, primary cause of kidney failure (diabetes, hypertension, glomerulonephritis, or other), Index of Coexistent Disease score (0-3), cardiovascular disease, congestive heart failure, left ventricular hypertrophy, diabetes, and serum albumin level (at baseline or year 1).
  • 46. Cardiovascular Mortality Cardiovascular Disease mortality by baseline urine output Cardiovascular Disease mortality by one-year urine output
  • 47. Mortality and Change in Urine Output
  • 50. Improvements CVD Mortality Not enough power? Many variables were very close to statistical significance Definition of Residual Renal Function Subjective urine output of >250cc rather arbitrary. Maybe we are mislabeling those with ~100 cc urine output/day as not having RKF when they do enjoy its protective effects
  • 51. Improvements More nit-picking than real concerns Diuretics shouldn’t increase RKF even though they do increase urine output (unless volume is the issue!) EPO usage was only calculated at baseline and 6 months, much earlier than the study stopped follow-up. Maybe not the best measure of residual endocrine kidney function
  • 52.
  • 53. Future studies may be useful to assess interventions aimed at preserving residual renal function
  • 54. As nephrologists, it is our responsibility to be advocates for the last few cc’s of GFR; they may be the difference between life and death…
  • 55. …or certainly a keg-stand and a picnic

Hinweis der Redaktion

  1. More questions than answers- which function of the kidney is most important?
  2. 11% decreased mortality with ~ 1cc/min/1.73m2. 10L/wk=1cc/min/1.73m2
  3. For each 1m./min/1.73m2 increase in eGFR was associated with a 12% lower mortality (RR 0.88) compared with zero rGFR
  4. rGFR is calculated as average of Renal creatinine clearance and renal nitrogen clearance (BUN)
  5. 5L/wk/1.73m2 = .49 cc/min/1.73m2, again 12% reduced mortality for every .5 cc/min/1.73m2 residual renal function [here GFR= native kidney]
  6. Entirely disappears when you factor in urine volume produced. Urine volume produced is the best prognosticator of mortality in PD patients. So maybe volume control and fluid shifting is more important than clearance
  7. European descent, relatively healthy, older (mean age 66), LAST POINT= Prevalence, not incidence
  8. 65% lower mortality within two years if patient produces > 100cc/day urine
  9. Delivered Kt/V split into quintiles in aneuric patients and in patients with RRF intact (urine>100cc/24h)
  10. RR 0.44 (56% decreased mortality) per 1 unit increase in the 1-week rKt/V during follow-up of 1.7 yrs. Data collected at month#3 and every 6 months thereafter. RR calculated on having renal function at given time t/ time of death? Which rKt/V was used for each patient?
  11. A positive Beta estimate indicates a beneficial effect; a negative Beta estimate indicates an unfavorable effect on a QoL dimension. For all dimensions shown, a higher rGFR was associated with a better QoL. For example, an increase in the rGFR with 10 mL/min/1.73 m 2was associated with an increase in the score for “Physical functioning” by 7.28. This difference on a scale ranging from 0 to 100 (Table 2) may be regarded as small but was highly significant (P = 0.0001). For the majority of the other dimensions the association with the rGFR was significant as well. The associations between pCrCl and QoL dimensions were either in a positive or negative direction, and no association was statistically significant at the 5% level.
  12. Preserved urine output more likely to be white, have higher systolic BP, higher pulse pressure at baseline, but only more likely to be white by year one.
  13. Late referral= < 4 mo between first nephrology evaluation and starting dialysis
  14. D Demographic characteristics: age, race (white or other), sex, educational status (completed high school or not), marital status (married or not), and employment status (employed or not employed).
  15. Highlight the statistically significant ones- most are not!
  16. The Endocrine Kidney